Protein gene product 9.5 is diagnostically helpful in delineating high-grade renal cell cancer involving the renal medullary/sinus region from invasive urothelial cell carcinoma of the renal pelvis.

The classification of poorly differentiated carcinomas involving the renal medullary/sinus region might be challenging on conventional histomorphologic grounds alone. However, delineation of high-grade renal cell carcinomas such as collecting duct (Bellini) carcinoma from urothelial cell carcinoma of the renal pelvis is critical, as it conveys important therapeutic implications. We assessed the so far neglected differential diagnostic role of protein gene product 9.5, a neuropeptide involved in intracellular proteolysis, in terms of differentiating invasive urothelial cell carcinomas of the renal pelvis from high-grade renal cell carcinomas infiltrating the renal medullary/sinus region. To this aim, 21 invasive urothelial cell carcinomas of the renal pelvis and 27 high-grade renal cell carcinomas (8 renal cell carcinomas with sarcomatoid dedifferentiation and 5 type 1 and 7 type 2 papillary renal cell carcinomas as well as 7 collecting duct carcinomas) were stained with antibodies directed against protein gene product 9.5, CD10, vimentin, CEA, p63, CK5/6, CK7, CK20, PAX2, PAX8, CD117 (c-Kit), AE1/3, α-methyl CoA racemase, actin, and desmin. Briefly, strong protein gene product 9.5 expression was observed in 6 (86%) of 7 collecting duct carcinomas, 8 (67%) of 12 papillary renal cell carcinomas, and 2 (25%) of 8 renal cell carcinomas with sarcomatoid dedifferentiation. Conversely, none of the 21 urothelial cell carcinomas investigated showed protein gene product 9.5 expression. Our findings suggest that protein gene product 9.5, particularly if used in conjunction with p63 and CK5/6, might be helpful in differentiating high-grade renal cell carcinomas from urothelial cell carcinomas of the renal pelvis, whereas its specificity with respect to the histologic subtyping of renal cell carcinomas seems to be low. However, because of the limited number of study cases enrolled in our investigation, our findings need to be validated in the future.